Angiogenesis is a complex process that plays a pivotal role in several human diseases, including cancers. A number of genes involved in vessel formation and maintenance have been identified and their functions characterized in a number of vertebrate species, including humans. Because the functions of many of these genes are conserved, animal models have been successfully used to study angiogenesis and identify genes involved in these processes. However, until recently, effective strategies for selectively repressing expression of specific genes and determining function have been limited to a few model organisms. This Phase I SBIR aims to develop the zebrafish as a model organism for angiogenesis target validation using a novel 'reverse genetics' approach. This approach can be used to examine the role of novel genes in angiogenesis as well as vessel maintenance. In addition, this approach may prove useful in generating gene 'knock down' in highly vascularized organs. The long-term goal of this project is to develop this approach as a tool for identifying the function of uncharacterized genes and evaluating their potential as therapeutic targets. PROPOSED COMMERCIAL APPLICATION: By providing a method for identifying angiogenesis targets, the zebrafish assay will facilitate the drug development process for cancer and heart disease.